Cross-dependence on ethanol and pentobarbital in rats reinforced on diazepam

Cross-dependence on ethanol and pentobarbital was studied in rats reinforced on diazepam, using an intravenous self-administration method. Five rats were allowed to self-administer diazepam 2.0 mg/kg per injection intravenously by pressing a lever on a continuous reinforcement schedule over a 20 day period. The total daily dose of diazepam delivered reached 50 mg/kg/day. Thereafter, ethanol (50 or 100 mg/kg per injection) and then pentobarbital (6 mg/kg per injection) were substituted for diazepam for 3 and 2 days, respectively. During these substitution periods, responding for self-administration, food intake and body weight were recorded. When ethanol was substituted, self-administration responding increased and then decreased. Food intake and body weight also decreased during this period. These changes during the ethanol substitution session resembled those observed during withdrawal sessions. In contrast, when pentobarbital was substituted, no significant changes in self-administration responses, food intake or body weight were seen. These findings suggest that diazepam produces cross-dependence on pentobarbital, but not on ethanol at the doses used in this experiment.